View source for 1ek1


==CRYSTAL STRUCTURE OF MURINE SOLUBLE EPOXIDE HYDROLASE COMPLEXED WITH CIU INHIBITOR==
<StructureSection load='1ek1' size='340' side='right'caption='[[1ek1]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ek1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EK1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EK1 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIU:N-CYCLOHEXYL-N-(4-IODOPHENYL)UREA'>CIU</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1cqz|1cqz]], [[1cr6|1cr6]], [[1ek2|1ek2]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.9 and 3.3.2.10 3.3.2.9 and 3.3.2.10] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ek1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ek1 OCA], [https://pdbe.org/1ek1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ek1 RCSB], [https://www.ebi.ac.uk/pdbsum/1ek1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ek1 ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/HYES_MOUSE HYES_MOUSE]] Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides. Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. Also determines steady-state levels of physiological mediators. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid, 12-phosphonooxy-octadec-9E-enoic acid, and p-nitrophenyl phospate (By similarity). 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ek/1ek1_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ek1 ConSurf].
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== Publication Abstract from PubMed ==
The structures of two alkylurea inhibitors complexed with murine soluble epoxide hydrolase have been determined by x-ray crystallographic methods. The alkyl substituents of each inhibitor make extensive hydrophobic contacts in the soluble epoxide hydrolase active site, and each urea carbonyl oxygen accepts hydrogen bonds from the phenolic hydroxyl groups of Tyr(381) and Tyr(465). These hydrogen bond interactions suggest that Tyr(381) and/or Tyr(465) are general acid catalysts that facilitate epoxide ring opening in the first step of the hydrolysis reaction; Tyr(465) is highly conserved among all epoxide hydrolases, and Tyr(381) is conserved among the soluble epoxide hydrolases. In one enzyme-inhibitor complex, the urea carbonyl oxygen additionally interacts with Gln(382). If a comparable interaction occurs in catalysis, then Gln(382) may provide electrostatic stabilization of partial negative charge on the epoxide oxygen. The carboxylate side chain of Asp(333) accepts a hydrogen bond from one of the urea NH groups in each enzyme-inhibitor complex. Because Asp(333) is the catalytic nucleophile, its interaction with the partial positive charge on the urea NH group mimics its approach toward the partial positive charge on the electrophilic carbon of an epoxide substrate. Accordingly, alkylurea inhibitors mimic features encountered in the reaction coordinate of epoxide ring opening, and a structure-based mechanism is proposed for leukotoxin epoxide hydrolysis.

Binding of alkylurea inhibitors to epoxide hydrolase implicates active site tyrosines in substrate activation.,Argiriadi MA, Morisseau C, Goodrow MH, Dowdy DL, Hammock BD, Christianson DW J Biol Chem. 2000 May 19;275(20):15265-70. PMID:10747889<ref>PMID:10747889</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1ek1" style="background-color:#fffaf0;"></div>

==See Also==
*[[Epoxide hydrolase 3D structures|Epoxide hydrolase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Hydrolase]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Argiriadi, M A]]
[[Category: Christianson, D W]]
[[Category: Dowdy, D L]]
[[Category: Goodrow, M H]]
[[Category: Hammock, B D]]
[[Category: Morisseau, C]]
[[Category: Alpha/beta hydrolase fold]]
[[Category: Disubstituted urea inhibitor]]
[[Category: Homodimer]]